Our previous studies have shown a dysregulation of innate immune responses in the oral mucosa of SIV infected rhesus macaques. We hypothesize that this dysregulation is, in part, associated with pathogenesis of the epithelium that emerges in primary acute infection, and leads to changes to the composition of the microflora that create a physiological niche for pathogenic species to invade. We will test this hypothesis by comparative analysis of the changes in innate immune response and barrier functions occurring within the tongue, oropharynx, and cheek pouch epithelium that occur during primary and chronic stage SIV infection in rhesus macaques. Alterations in the oral microbiome during the course of SIV infection will be characterized as to relationship to changes in expression of antimicrobial factors in the epithelial layer, and their potential role in the development of opportunistic secondary infections in the oral cavity. Data from the proposed studies will also be utilized to initiate the establishment of a Simian Oral Microbiome Database (SOMD) for non-human primates, and to develop a Simian Oral Microbe Identification Microarray (SOMIM) to rapidly assess the oral microbial profiles of rhesus monkeys in future studies covering a variety of oral infections or conditions. The project will coordinate comprehensive cellular and molecular assays in a highly controlled experimental environment. The results will increase our understanding of the molecular mechanisms in the host epithelium that contribute to the shift of resident oral microflora to diseased state oral microflora, and provide potential biomarker targets for future therapeutic advances that focus on preventing or curing opportunistic secondary infections in HIV infected patients PUBLIC HEALTH RELEVANCE: ,Innate immunity and alteration of the oral microbiome in SIV infected rhesus macaques We are analyzing changes in host immune responses and protective functions of the oral epithelial layer that result from simian immunodeficiency virus (SIV) infection. We will determine if these changes emerge in the early, primary stage of infection, and how the changes impact the composition of the resident bacterial microflora in the oral cavity and correlate with the onset of secondary opportunistic infections.